Transdermal or intradermal delivery of drugs, including protein and vaccine delivery, is a very effective method for achieving systemic or localized pharmacological effects. However, there are barriers involved in providing sufficient drug penetration across the skin. Skin consists of multiple layers. The stratum corneum is the outermost layer, then there is a viable epidermal layer, and finally a dermal tissue layer. The thin layer of stratum corneum of 10-50 μm represents a major barrier for drug delivery through the skin. The stratum corneum is responsible for 50%-90% of the skin barrier property against transdermal drug delivery, depending upon the physical and chemical properties of the drug material, in particular, lipophilicity and molecular weight.
The use of microneedles in transdermal and intradermal delivery is advantageous as intracutaneous drug delivery or drug sampling can be accomplished by reducing the above barrier without pain and bleeding. As used herein, the term “microneedles” refers to a plurality of elongated structures that are sufficiently long to penetrate through the stratum corneum skin layer into the epidermal or dermal or subcutaneous layer. In general, the microneedles are not so long as to penetrate into the dermal layer, although there are circumstances where penetrating the dermal layer would be necessary or desirable. The use of microneedles as an alternative to the use of hypodermic needles for drug delivery by injection is disclosed in U.S. Pat. No. 3,964,482, in which an array of either solid or hollow microneedles is used to penetrate through the stratum corneum and into the epidermal layer. Fluid is dispensed either through the hollow microneedles or through permeable solid projections, or perhaps around non-permeable solid projections that are surrounded by a permeable material or an aperture. A membrane material is used to control the rate of drug release, and the drug transfer mechanism is absorption.
Other types of microneedle and microblade structures are disclosed in PCT Publications Nos. WO 98/00193, WO 97/48440, WO 97/48441, WO 97/48442 and WO 96/37256. Microneedles (less than 1 mm in diameter) have been used to effect percutaneous drug delivery. Microneedles have also been used to deliver a drug through a lumen in the needles, to deliver a drug along the outside of the needle shafts, or as skin perforators for subsequent patch drug application. Silicon microneedles, for example, have been developed using the microfabrication method or MicroElectroMechanicalSystems (MEMS) fabrication method. Examples are described in U.S. Pat. Nos. 6,334,856, 6,256,533, 6,312,612 and 6,379,324. Unfortunately, silicon needles are not dissolvable in the skin, can break during use and stay in the skin tissue, producing considerable irritation and even infection. Non-silicon microneedles have also been developed. Examples are described in U.S. Pat. Nos. 6,334,856 and 6,091,975. However, microneedles that are made of metal or plastic are insoluble or slowly dissolve (i.e., in less than several hours) in the skin, and are therefore generally used for providing a microconduit to transport drug from a drug reservoir, or for creating micropores.
Typically, microneedles are fabricated by the MEMS fabrication method. The use of polydimethylsilozane (PDMS) mold for casting polymeric microneedles is disclosed in U.S. Pat. Nos. 6,663,820 and 6,334,856 in which the positive matter of microneedles is fabricated by using MEMS technology. However, MEMS fabrication for the master microneedle array can be expensive and complicated. Moreover, the polymeric microneedles may require drug loading or drug coating, rendering the casting methods unsuitable for mass production.